Long-term stimulation by active epiretinal implants in normal and RCD1 dogs

Abstract

An epiretinal prosthesis, consisting of an extraocular microelectronic stimulator and an intraocular electrode array, was implanted in one eye of three blind and three sighted dogs. Three dogs (2 blind, 1 normal) were stimulated for 120 days, and two dogs (both normal) for 60 and 103 days respectively for 8-10 h/day at levels of 0.1 mC cm(-2) and 0.05 mC cm(-2), with each stimulus level presented to half of the array. One blind dog was kept as an inactive implant control. During the study period, electroretinograms (ERG) and fundus photographs were recorded. At the end of the study period, the dogs were sacrificed and histological and morphometric evaluation was made of the retina. No inflammatory reaction, neovascularization or hemorrhage was observed during the follow-up examinations. ERGs were unchanged. Stimulus levels used were of sufficient amplitude to elicit cortical evoked potentials. Histological evaluation showed no inflammatory infiltrates or changes in retina morphometry related to electrical stimulation when compared to the unstimulated control eye. Morphometric analysis revealed no consistent differences relating to electrical stimulation. In summary, chronic electrical stimulation of the dog retina at up to 0.1 mC cm(-2) with an epiretinal prosthesis does not appear to adversely affect the retina.

High-Resolution Electrical Stimulation of Primate Retina for Epiretinal Implant Design

“…Such stimulation attempts use much larger electrodes (125-500 m) and/or long-duration stimulation pulses (ϳ1 ms), and result in multiple evoked spikes at long latencies (ϳ10 ms). With these stimulation configurations, spike thresholds are typically much higher than the direct-activation values reported in this study (Jensen et al, 2003;Suzuki et al, 2004;Guven et al, 2005;Jensen and Rizzo, 2007;Ye and Goo, 2007). Results from the present study are most comparable with recently published reports of epiretinal stimulation that activated ganglion cells directly by using small electrodes and short pulses: 0.05-0.31 mC/cm 2 for 40 m disk electrodes in frog retina (Kuras et al, 2004), 0.14 -0.25 mC/cm 2 for 30 m cone-shaped electrodes in rabbit retina (Fried et al, 2006), and 0.02-0.20 mC/ cm 2 for 8 -12 m disk electrodes in rat retina (Sekirnjak et al, 2007).…”

A review of in vivo animal studies in retinal prosthesis research

“…The species involved include rats (n=6) [26,29,76,80,81,96], rabbits (n=14) [33,36,42,72,73,90,94,95,102,103,105,106,116,121], cats (n=18) [18, 19, 21-23, 30, 32, 43, 78, 79, 82, 93, 98, 99, 101, 114, 117, 120], dogs (n=4) [16,39,40,66], sheep (n=1) [51] and pigs/minipigs (n=9) [34,42,49,59,69,91,92,100,102]. Two papers [16,26] which involved three animal species do not figure in Table 2 due to lack of space, but are discussed in the review.…”

“…Retinal dystrophy in the Irish setter (RCD1 mutation) has been studied for over 20 years [3-5, 12, 87]. Retinal stimulation studies have been successfully conducted with this model [16,39,40,66]. The Briard beagle carries a well-characterized retinal dystrophy [6,113].…”

“…Dogs are expensive to house, in particular because the retinal degeneration takes several months to develop (in RCD1 dogs, the ERG extinguishes at approximately 18 weeks) [66]. We found three canine studies in which implantbiocompatibility and biostability [39,40,66] and one study in which electrically elicited responses (EERs) produced by epiretinal stimulation [16] were examined.…”

A Neurostimulator Design for Long-term Animal Experiments

“…The neural prosthetics, such as cochlear implant or retinal prosthesis, needed a wired or a wireless external component to provide stimulation parameters and power to the internal electrodes [1,2]. When those systems were used for long-term electrical stimulation in animals [3,4], there were many problems that needed to be solved. Systems with a percutaneous connection to the external portion restricted the animals' movement and posed an infection risk.…”